Investigation of sodium phenylbutyrate (NaPB) as a chemical chaperone for the treatment of Mct8-deficient mouse models

• Applicants: Dr. Doreen Braun; Professor Dr. Ulrich Schweizer
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 455336044

The monocarboxylate transporter 8 (MCT8) is a specific transporter for thyroid hormones widely expressed in cells and tissues. Inactivating mutations in MCT8 lead to severe psychomotor retardation. At the moment, there is no adequate therapy to treat MCT8 deficiency.Mice deficient in Mct8 and Oatp1c1 replicate several features of MCT8 deficient patients. Treatment options rely on thyromimetic agents and are tested in Mct8/Oatp1c1 double-deficient mice.Sodium phenylbutyrate (NaPB) is a chemical chaperone that rescues the function of several pathogenic MCT8 mutations in an over-expressing cell model and differentiated human induced pluripotent stem cells (iPSC).Here we want to investigate the effect of NaPB in three mouse models carrying different pathogenic Mct8 point mutations.

• DFG Programme: Research Grants